The role of cyclic AMP in pancreatic secretion has not yet clearly been demonstrated. We have studied the role of cyclic GMP in pancreatic enzyme secretions in guinea pig pancreatic slices. We have shown that various agents (caerulein, carbamyl choline, cholocystokinin-octa peptide) that cause increase in pancreatic enzyme secretions do so by increasing intracellular cyclic GMP in the pancreatic acinar cells. This increase in cyclic GMP appears to be mediated by the increase in flux of calcium. The calcium ionophore, A23187, also causes a marked increase in cyclic GMP with a concomitant increase in amylase release. It is also possible to increase amylase secretion by dibutyryl cyclic GMP. From these studies it appears that various hormones and agents cause amylase secretion by increasing cyclic GMP in the cell by increasing Ca2 ion flux.